Pathophysiology of Atheroma

Question 1

What is an Atheroma/Atherosclerosis?

Answer 1

Formation of focal elevated lesions (plaques) in intima of large and medium sized arteries

Question 2

What can an atheromatous plaque in coronary arteries lead to?

Answer 2

Ischaemia

Question 3

What is the serious consequence of atheroma in coronary artery?

Answer 3

Angina due to myocardial ischaemia

Question 4

Explain arteriosclerosis

Answer 4

Not atheromatous
Age-related change in muscular arteries

Question 5

What happens in arteriosclerosis?

Answer 5

Smooth muscle hypertrophy, apparent reduplication of internal elastic laminae, intimal fibrosis - leads to decreased vessel diameter

Question 6

When are clinical effects of arteriosclerosis more apparent?

Answer 6

When CVS is further stressed by haemorrhage, major surgery, infection and shock

Question 7

What does the normal artery wall consist of?

Answer 7

Intima includes endothelium
Separated by internal elastic lamina
Media
Separated by external elastic intima
Adventitia

Question 8

Describe the fatty streak in atheroma?

Answer 8

Earliest significant lesion, usually young children.
Yellow linear elevation of intimal lining and masses of lipid laden macrophages

Question 9

What is the clinical significance of fatty streak atheroma?

Answer 9

No clinical significance
May disappear
Patients at risk of atheromatous plaque

Question 10

Describe the early atheromatous plaque in atheroma?

Answer 10

Young adult onwards
Smooth yellow patches in intima and lipid-laden macrophages
Progress to established plaques

Question 11

Describe fully developed atheromatous plaque in atheroma?

Answer 11

Central lipid core with fibrous tissue cap covered by arterial endothelium
Collagens in cap for strength
Inflammatory cells reside in fibrous cap

Question 12

What inflammatory cells reside in fibrous cap and where are they recruited from?

Answer 12

Macrophages, T-lymphocytes and mast cells
Recruited from arterial endothelium

Question 13

Describe a fully developed atheromatous plaque in atheroma?

Answer 13

Central lipid core rich in cellular lipids/debris derived from macrophages (died in plaque)
Soft, highly thrombogenic, often rim of foamy macrophages

Question 14

What makes macrophages foamy?

Answer 14

Uptake of oxidised lipoproteins via specialised membrane bound scavenger receptor

Question 15

What occurs late in plaque development?

Answer 15

Dystrophic calcification extensive - marker for atherosclerosis in angiograms and CTs
Form at arterial branching points/ bifurcations which can cause turbulent flow
Late stage plaques can cover large areas and confluent

Question 16

What are the features of an established atheromatous plaque?

Answer 16

Lipid-rich core
Fibrous cap

Question 17

Explain complicated atheroma?

Answer 17

Has features of established atheromatous plaque plus haemorrhage into plaque (calcification), plaque rupture/fissuring or thrombosis

Question 18

What is the most important risk factor of atheroma?

Answer 18

Hypercholesterolaemia

Question 19

What does hypercholesterolaemia cause?

Answer 19

Causes plaque formation and growth in absence of other known risk factors

Question 20

What happen when there is a decrease un functional receptors on cell surfaces?

Answer 20

elevated plasma LDL cholesterol levels

Question 21

What happens if patient has rare homozygous mutation causing hypercholesterolaemia?

Answer 21

Much higher cholesterol levels and usually die from coronary artery atheroma in teens/infancy

Question 22

What are signs of major hyperlipidaemia?

Answer 22

Familial/primary or acquired/secondary
Biochemical evidence
Corneal arcus
Tendon xanthomata
Xanthelasmata
Premature, FH of MI/atheroma

Question 23

What is Xanthelasmata?

Answer 23

Collections of foamy macrophages and lipids in skin
Often under eyes and are yellow plaques

Question 24

What are some risk factors for atheroma?

Answer 24

Smoking, hypertension, diabetes mellitus, male, elderly
These accelerate process of plaque formation driven by lipids

Question 25

What is the 2 step process of developing atheromatous plaques?

Answer 25

1. injury to endothelial lining of the artery 2. Chronic inflammation and healing of vascular wall to agent causing injury

Question 26

Describe the pathogenesis of atherosclerosis

Answer 26

Endothelial injury and dysfunction Accumulation of lipoproteins (LDL) in vessel wall Monocyte adhesion - migration into intima and transformation to foamy macrophages Platelets adhesion Factor release from activated platelets and macrophages recruit smooth muscle cell Smooth cell proliferation, EXM production and T-cell recruitment Lipid accumulation

Question 27

What are the most important endothelium injuries causing atheroma?

Answer 27

Haemodynamic disturbances causing turbulent flow instead of smooth Hypercholesterolaemia

Question 28

How does hypercholesterolaemia cause endothelium impair?

Answer 28

Increasing production of reactive O2 species Lipoproteins aggregate in intima and are modified by free radicals which are produced from inflammatory cells This leads to modified LDL accumulation by macrophages - foamy macrophages then toxic to endothelial cells

Question 29

How are injured endothelial cells functionally altered?

Answer 29

Enhanced expression of cell adhesion molecules High permeability for LDL Increased thrombogenicity

Question 30

Describe the formation of advanced plaque formation

Answer 30

Large numbers macrophages and T lymphocytes Lipid-laden macrophages die through apoptosis lead lipid into lipid core Response to injury - chronic inflammatory process Growth factors (PDGF) Fibrous cap encloses lipid rich core

Question 31

What is the chronic inflammatory process?

Answer 31

1. inflammatory reaction 2. process of tissue repair

Question 32

Where are growth factors secreted from?

Answer 32

By platelets, injured endothelium, macrophages and smooth muscle cells

Question 33

What does secretion of growth factors (PDGF) cause?

Answer 33

Proliferation intimal smooth muscle cells, subsequent synthesis collagen, elastin and mucopolysaccharide

Question 34

What does microthrombi formed at denuded areas of plaque surface lead to?

Answer 34

Organised by same repair process (smooth muscle cell invasion and collagen deposition)

Question 35

Established plaques and plaque growth are also initiated by?

Answer 35

Small areas of endothelial loss

Question 36

What are some clinical consequences of atheroma?

Answer 36

Progressive lumen narrowing due to high grade plaque stenosis Acute atherothrombotic occlusion Embolisation of distal arterial bed Ruptured atheromatous abdominal aortic aneurysm

Question 37

Describe progressive lumen narrowing due to high grade plaque stenosis?

Answer 37

Stenosis of more than 50-75% of vessel lumen leads to critical reduction of blood flow in distal artery so can get reversible tissue ischaemia

Question 38

What can a stenosed atheromatous coronary artery cause?

Answer 38

Stable angina

Question 39

What does very serious stenosis lead to?

Answer 39

Ischaemic pain at rest - unstable angina Ex. ileal, femoral, popliteal artery stenosis Longstanding tissue ischaemia

Question 40

Describe acute atherothrombotic occlusion

Answer 40

Rupture of plaque - exposes highly thrombogenic plaque contents to blood stream - activation of coagulation cascade and thrombotic occlusion in very short time

Question 41

What does total occlusion lead to?

Answer 41

Irreversible ischaemia then necrosis of tissues which is infarction Ex. MI, stroke, lower limb gangrene

Question 42

Describe embolisation of the distal arterial bed

Answer 42

Detachment of small thrombus fragments from thrombosed atheromatous arteries - embolise distal to ruptured plaque Embolic occlusion of small vessels - small infarcts of organs

Question 43

What are some examples of embolisation of the distal arterial bed?

Answer 43

Carotid artery atheromatous debris can lead to stroke as cerebral infarct Cholesterol emboli in kidney, leg and skin due to large ulcerating aortic plaques Life threatening arrhythmias due to small foci of necrosis in heart

Question 44

Describe ruptured atheromatous abdominal aortic aneurysm?

Answer 44

Media beneath atheromatous plaques gradually weakened - gradual dilatation of vessels Is slow but progressive, seen in elderly Sudden rupture - retroperitoneal haemorrhage Aneurysms > 5cm which are at high risk of rupture Mural thrombus - emboli to legs

Question 45

What are signs of a vulnerable plaque?

Answer 45

Typically thin fibrous cap, large lipid core and prominent inflammation Pronounced inflammatory activity - degradation and weakening of plaque - increase risk of plaque rupture

Question 46

What do plaque inflammatory cell secrete?

Answer 46

Proteolytic enzymes, cytokines and reactive oxygen species

Question 47

What are the preventative and therapeutic approaches?

Answer 47

Stop smoking Control blood pressure Weight loss Regular exercise Dietary modifications

Question 48

What are secondary prevention options?

Answer 48

Cholesterol lowering drugs which inhibit platelet aggregation of decrease risk of thrombosis on established atheromatous plaques

Question 49

What are surgical options?

Answer 49

To remove or bypass atheromatous vessels